Regulation and therapeutic potential of NLRP3 inflammasome in intestinal diseases

J Leukoc Biol. 2025 Apr 23;117(4):qiaf014. doi: 10.1093/jleuko/qiaf014.

Abstract

The NOD-like receptor family, particularly the protein 3 that contains the pyrin domain (NLRP3), is an intracellular sensing protein complex responsible for detecting patterns associated with pathogens and injuries. NLRP3 plays a crucial role in the innate immune response. Currently, a wide range of research has indicated the crucial importance of NLRP3 in various inflammatory conditions. Similarly, the NLRP3 inflammasome plays a significant role in preserving intestinal balance and impacting the advancement of diseases. In addition, several randomized trials have demonstrated the safety and efficacy of targeting NLRP3 in the treatment of colitis, colorectal cancer, and related diseases. This review explores the mechanisms of NLRP3 assembly and activation in the gut. We describe its pathological significance in intestinal diseases. Finally, we summarize current and future therapeutic approaches targeting NLRP3 for intestinal diseases.

Keywords: NLRP3; activation; intestinal disease; intestinal epithelial barrier; intestinal immunity; pharmacological targeting.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammasomes* / metabolism
  • Intestinal Diseases* / drug therapy
  • Intestinal Diseases* / immunology
  • Intestinal Diseases* / metabolism
  • Intestinal Diseases* / pathology
  • Intestinal Diseases* / therapy
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Inflammasomes
  • NLRP3 protein, human